Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptide (CGRP) is a neurotransmitter present in the peripheral ends of sensory neurons of the gut and may modulate reflexes of the enteric nervous system. We studied the release of CGRP in normal human gallbladders and in those containing gallstones to test the hypothesis that abnormalities of regulation of CGRP release participate in gallstone formation. Human gallbladder strips were obtained from histologically normal organs removed during liver surgery (n = 8) or from patients operated upon for symptomatic cholelithiasis (n = 14). After removal of the mucosa, muscle strips were superfused with oxygenated Kreb's buffer in an organ bath at 37 degrees C. Pharmacologic agents were added to the superfusate and samples were collected at 2-min intervals for analysis. CGRP release was measured by a sensitive and specific radioimmunoassay and adjusted for tissue weight. In normal gallbladders, CGRP release was stimulated sixfold over basal by capsaicin (10(-5) M) to 363 +/- 75 pg per gram of muscle per 2 min. This release was abolished by addition of somatostatin (SS) or the neural blocker tetrodotoxin (TTX). Lesser degrees of CGRP release were observed after nonspecific stimulation with K+ or phosphodiesterase inhibition with caffeine. In gallbladders with gallstones, capsaicin-induced CGRP release was 74 +/- 16 pg per gram of muscle per 2 min (20% of normal, P < 0.001). Release induced by caffeine and K+ was also inhibited compared to normal gallbladder strips. Release of CGRP from diseased strips was abolished by TTX and inhibited by SS to degrees similar to normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired release of gallbladder calcitonin gene-related peptide in human gallstone disease. 779 41

Male F344 rats fed ad libitum or maintained on 60% of the ad libitum food intake were sacrificed at 6, 12, 18 and 24 months of age. The thyroids were removed for the analysis of the C-cell hormones, calcitonin, calcitonin gene-related peptide (CGRP) and somatostatin. In the animals fed ad libitum, the peptide content of all three hormones and their mRNA pools increased significantly with age. The increases were markedly suppressed by food restriction. Similarly, the rate of mRNA synthesis of the hormones increased with age and was attenuated by food restriction. Calcitonin and CGRP containing cells increased in number with age in the ad libitum fed animals. In the food restricted animals the numbers of calcitonin positive cells were consistently but not significantly lower than those of ad libitum fed animals at similar ages. In the case of CGRP containing cells, their numbers were significantly lower in the food restricted than in the ad libitum fed animals from 18 months of age. Our findings indicate that aging and food restriction modulate the levels of the thyroidal C-cell hormones at the levels of cell proliferation and possibly gene transcription.
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PMID:Evaluation of the molecular and cellular basis for the modulation of thyroid C-cell hormones by aging and food restriction. 790 59

Calcitonin gene-related peptide (CGRP)-I has been reported to inhibit gastric acid secretion through stimulation of gastric somatostatin-14 (S-14) release. To establish whether some of the effects of CGRP-I on intestinal function might also be mediated through somatostatin, fetal rat intestinal cultures were treated with test agents for 2 h, and the secretion of somatostatin-like immunoreactive (SLI) peptides was determined by RIA. The intestinal cultures have been previously found to synthesize and secrete both major forms of intestinal somatostatin (S-28 and S-14). Rat (r) CGRP-I treatment of the intestinal cultures stimulated SLI secretion to 163 +/- 33% of the control level at 3.3 x 10(-7) M (P < 0.01) and 227 +/- 30% of the control level at 10(-6) M (P < 0.001). In contrast, the structurally related peptide, human CGRP-II, had no effect on total SLI release at any concentration up to 10(-6) M. Gel permeation chromatography revealed that rCGRP-I increased the secretion of S-14 by 22 +/- 6-fold (P < 0.01) compared to the control value, whereas that of S-28 increased nonsignificantly by only 2 +/- 1-fold. Thus, the ratio of S-28 to S-14 secreted into the medium decreased from 1.7 +/- 0.2 in control medium to 0.2 +/- 0.3 after rCGRP-I treatment (P < 0.01). As the ratio of S-28 to S-14 stored by the cells was not altered by rCGRP-I treatment, these findings suggest that intestinal S-28 and S-14 may be secreted by two distinct intestinal D-cells with different sensitivities to rCGRP-I or by a single D-cell type containing distinct pools of S-14 and S-28 that have different sensitivities to rCGRP-I. The results of these in vitro studies further indicate that in vivo, CGRP-I may modulate aspects of intestinal function through its stimulation of the secretion of S-14.
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PMID:Calcitonin gene-related peptide-I preferentially stimulates secretion of somatostatin from intestinal cultures. 790 70

Calcitonin gene-related peptide (CGRP), a potent vasodilating peptide, is present in primary afferent neurons of the gastric mucosa. However, its functional role in the stomach is not well established. The present study was undertaken to elucidate the involvement of gastric CGRP in the mechanism of protection against mucosal damage. Newborn Wistar rats were made CGRP-deficient by intraperitoneal injection of a sensory neurotoxin, capsaicin. All the experiments were performed 2.5 months after birth. The formation of mucosal lesions by administration of indomethacin to CGRP-deficient rats was significantly enhanced in comparison with that in normal rats. Intragastric administration of capsaicin significantly reduced the indomethacin-induced gastric mucosal lesions in normal rats. Pretreatment with a CGRP antagonist abolished the protective action of intragastric capsaicin against damaging agents. In isolated perfused stomach from normal rats, acute arterial infusion of capsaicin significantly reduced the perfusion pressure of the left gastric artery, with a simultaneous increase in CGRP and somatostatin secretion. The reduction of perfusion pressure and the increase of somatostatin secretion were inhibited by concomitant administration of a CGRP antagonist. In contrast, capsaicin infusion had no effect in CGRP-deficient rats. These results suggest that CGRP in the stomach plays a pivotal role in protection against gastric mucosal damage by indomethacin, possibly through an increase in gastric blood flow and somatostatin secretion.
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PMID:Calcitonin gene-related peptide: a neurotransmitter involved in capsaicin-sensitive afferent nerve-mediated gastric mucosal protection. 790 85

No satisfactory medical therapy exists for the treatment of primary hyperparathyroidism. Calcitonin and diphosphonates do not give good long-term control. This work examines the efficacy of the somatostatin analogue octreotide in the management of hyperparathyroidism. Twenty-one patients were admitted before parathyroid surgery and were treated for 6 days with subcutaneous octreotide 100 micrograms twice daily. Fasting blood samples were taken for determination of serum levels of calcium and parathyroid hormone, and 24-h urinary calcium excretion was measured before and after treatment. A significant decrease in urinary calcium was demonstrated, but the reduction in serum calcium level was not statistically significant and there was no change in serum parathyroid hormone concentration. Octreotide may provide therapy for patients with hyperparathyroidism and for those who have undergone unsuccessful neck exploration or who are unfit for operation. It may ameliorate hypercalciuria and reduce stone formation. The octapeptide may also have a potential role as a diagnostic test in primary hyperparathyroidism by determining the symptomatic effect of reducing raised levels of serum and urinary calcium.
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PMID:Somatostatin and primary hyperparathyroidism. 795 42

The studies were performed on cultured TT cells originating from human thyroid medullary carcinoma (i.e., from parafollicular cells of the thyroid). The amount of released calcitonin was dependent upon calcium level in the medium. Moreover, calcitonin secretion might be regulated by medium supplementation with polypeptide hormones. Somatostatin inhibited while glucagon and pentagastrin stimulated calcitonin secretion to t he medium. Calcitonin secretion was also influenced by biogenic amines and their precursors. Dihydroxy-1-phenylalanine and serotonin augmented while 5-hydroxy-1-tryptophan and dopamine inhibited calcium secretion. This, calcitonin secretion may be controlled by different substances present in the healthy organism. This points to a complex control of calcium ion level in the blood.
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PMID:Regulation of calcitonin secretion by thyroid parafollicular cells in vitro. 861 73

Calcitonin gene related peptide (CGRP), substance P (SP), and somatostatin (SOM) are probably the three most important sensory neuropeptides. However, in contrast to CGRP immunoreactivity (IR), SP- and SOM-IR occur also in neurons intrinsic to the dorsal horn. Colocalization of either SP- or SOM-IR with CGRP-IR is, therefore, strongly suggestive of a primary sensory origin. In this study, high resolution double-labelling immunocytochemistry was applied to detect CGRP/SP and CGRP/SOM colocalizations in axonal boutons of the rat superficial dorsal horn. Most boutons colocalizing CGRP-IR and SP-IR were not part of synaptic glomeruli. However, 15% of such boutons represented the central varicosities of type I synaptic glomeruli. CGRP-IR was always present in the small proportion of type I glomeruli central boutons that displayed SOM-IR. In a study in the cat combining double-labelling immunocytochemistry with intracellular injection of electrophysiologically characterized neurons, we found that nociceptive neurons received numerous synapses from varicosities colocalizing SP-IR and CGRP-IR. In contrast, non-nociceptive neurons almost completely lacked synaptic input from boutons colocalizing both immunoreactivities. This study confirms that fibres colocalizing SP-IR and CGRP-IR probably play a major role in spinal nociceptive mechanisms.
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PMID:Ultrastructural features of the colocalization of calcitonin gene related peptide with substance P or somatostatin in the dorsal horn of the spinal cord. 884 34

The distribution of peptide-containing nerve fibers and the effect of their neuropeptides on motor activity were studied in the muscularis mucosae of the guinea-pig proximal colon. In the immunohistochemical study, it was shown that the tachykinin (TK)-containing nerve fibers densely innervated the muscularis mucosae. In the superfusion study, three kinds of TKs, i.e., neurokinin A (NK-A), neurokinin B (NK-B) or substance P (SP), enhanced the spontaneous activity on the strips of muscularis mucosae with a tetrodotoxin (TTX)-insensitive manner. Their potency was in the rank order of NK-A > SP. This suggests that the muscle has a predominant NK2 receptor. Calcitonin gene-related peptide (CGRP)-immunoreactive fibers were commonly observed in the muscle. CGRP induced a potent inhibition on spontaneous activity and a concentration-dependent inhibition on the NK-A-elicited excitation in the presence of TTX, indicating its direct effect on the receptor in the muscle. On the other had, gastrin releasing peptide (GRP), galanin, neuropeptide Y or somatostatin were more or less immunopositive in nerve fibers, but they had no effect on the motility of the muscle except that GRP sometimes showed a faint increase in spontaneous activity. Neither methionine-enkephalin nor gastrin-17/cholecystokinin was immunoreactive and had any effect on the muscle. These neuropeptides other than TKs and CGRP do not seem to be neuromediators of motor activity of muscularis mucosae. The results suggest the possibility that TK-, especially NK-A- and CGRP-containing neurons, participate in the regulation of motor activity of the muscularis mucosae in the guinea-pig proximal colon.
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PMID:Distribution of several gut neuropeptides and their effects on motor activity in muscularis mucosae of guinea-pig proximal colon. 920 29

This study was undertaken to determine the segmental organization of the dorsal root ganglion (DRG) cells that give rise to pancreatic afferents containing a certain neuropeptide in the rat. These cells were examined using retrograde tracing combined with immunohistochemistry. Injection of horseradish peroxidase (HRP) into the pancreas resulted in the labeling of cells in bilateral T5-L2 DRGs, with most labeled cells lying at T10-T11. Injection into the duodenal (right), splenic (left), and entire lobes consistently produced more labeled cells significantly in the right, left, and right DRGs, respectively. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, somatostatin (SOM)-, and galanin (GAL)-immunoreactive (IR) cells in the DRGs (T9-T12) were found in -52, 17, 8, and 6%, respectively, but neuropeptide Y- and vasoactive intestinal polypeptide-IR cells were not found. About 88% of HRP-labeled cells in DRGs (T9-T12) contained CGRP, and approximately 16% of them contained SP. Although SOM- and GAL-IR cells were localized in the DRGs, these cells innervating the pancreas could not be found. In brief, these results show that bilateral (not similar in cell number on each side) DRG cells innervate the duodenal or splenic pancreas, and the majority of these cells that project to the pancreas contain CGRP and SP.
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PMID:Afferent innervation of the rat pancreas: retrograde tracing and immunohistochemistry in the dorsal root ganglia. 943 67

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.
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PMID:Neurogenic vasodilatation and plasma leakage in the skin. 945 75


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